Green Route for Amoxicillin Production Through the Integration With the Recycle of the by-Product (P-Hydroxyphenylglycine)

Pereira, Sandra Cerqueira; Castral, Thaís Corrêa; Ribeiro, M. P. A.; Giordano, R. L. C.; Giordano, Roberto

doi:10.5151/chemeng-cobeq2014-1263-20189-138533

Cited by 3 publications

(2 citation statements)

References 8 publications

(9 reference statements)

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“…For VD3, the photo-high-p,T process described by Escribà-Gelonch et al − was considered; for vitamin C, the two-step fermentation described by Lim et al; and for choline, the US3373201 patent . For paracetamol, the process starting from hydroquinone by Joncour et al was used, and for ibuprofen, the process according to US4981995; and the green route for amoxicillin production with a recycling integration described by Pereira et al The selection criterion of methodologies was to consider the current most circular and greenest process described, so the most advantageous process in terms of sustainability, which can give longer-term impact to this study, since industries need to move toward circularity.…”

Section: Resultsmentioning

confidence: 99%

Circular Economy Metrics for the Photo-High-p,T Continuous Multistep Synthesis of Vitamin D₃

Escribà‐Gelonch

Bricout

Hessel

2021

ACS Sustainable Chem. Eng.

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The vitamin D 3 flow-chemical process is a good route for exercising circularity in chemistry; as the complex chemistry of this reaction limits the highest yield to only 25%, a recycling operation becomes mandatory. In this context, this research applies, for the first time, a circular economy assessment to a flow chemistry process, including reaction and separation. This is undertaken on the example of the photo-flow-chemical synthesis of vitamin D 3 , previously developed by our group. In the research reported here, we develop a separation process to recycle the unreacted starting material 7-dehydrocholesterol after the photo-flow irradiation. We use acetonitrile for separation, instead of methanol, in the industrial process. In just one run, 90% of vitamin is extracted using dry acetonitrile as a separation solvent at 30 °C. A cumulative extraction efficiency of >99% is achieved after a second extraction step. The acetonitrile separation process connects directly to the subsequent vitamin crystallization using the same solvent. This eliminates the need to evaporate methanol in the industrial process; rather, the product is obtained just by cooling down. The Material Circular Indicator has been used as a central metric, and we needed to redefine this circularity metrics proposed by the Ellen MacArthur Foundation's CE100 program to the world of flow chemistry. Rather than being able to take the parameter of lifetime and utility used in the original C100 definition, the frequency and dose of usage of medicinal products are taken here, both of which are connected to chemical productivity and waste generation. To explore the application of this adapted methodology to other pharmaceutical production processes, the results for the proposed vitamin D 3 flow-chemical process are compared with five processes for producing vitamins, painkillers, and an antibiotic. It is shown that the vitamin D 3 flow chemistry process with the new separation achieves a Material Circular Indicator of 0.94, a recycled fraction mass above 0.95, and an energy demand reduction by a factor of 2.

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Section: Resultsmentioning

confidence: 99%

Circular Economy Metrics for the Photo-High-p,T Continuous Multistep Synthesis of Vitamin D₃

Escribà‐Gelonch

Bricout

Hessel

2021

ACS Sustainable Chem. Eng.

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“…Minimising feedstock consumption in different cases can lead to possible process configurations where reagents and solvent are recycled following desired product (amoxicillin) crystallisation [23,24]. Although recycling options are not explicitly considered in this work, they have been demonstrated in the literature for β-lactam antibiotic synthesis with nanofiltration for by-product (PHPG) removal [25]. This can allow for processes with greater material efficiencies and overall sustainability.…”

Section: Dynamic Optimisationmentioning

confidence: 99%

Dynamic Modelling and Optimisation of the Batch Enzymatic Synthesis of Amoxicillin

et al. 2019

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Amoxicillin belongs to the β-lactam family of antibiotics, a class of highly consumed pharmaceutical products used for the treatment of respiratory and urinary tract infections, and is listed as a World Health Organisation (WHO) "Essential Medicine". The demonstrated batch enzymatic synthesis of amoxicillin is composed of a desired synthesis and two undesired hydrolysis reactions of the main substrate (6-aminopenicillanic acid (6-APA)) and amoxicillin. Dynamic simulation and optimisation can be used to establish optimal control policies to attain target product specification objectives for bioprocesses. This work performed dynamic modelling, simulation and optimisation of the batch enzymatic synthesis of amoxicillin. First, kinetic parameter regression at different operating temperatures was performed, followed by Arrhenius parameter estimation to allow for non-isothermal modelling of the reaction network. Dynamic simulations were implemented to understand the behaviour of the design space, followed by the formulation and solution of a dynamic non-isothermal optimisation problem subject to various product specification constraints. Optimal reactor temperature (control) and species concentration (state) trajectories are presented for batch enzymatic amoxicillin synthesis.Processes 2019, 7, 318 2 of 17 worldwide [11]. The demonstrated enzymatic synthesis of amoxicillin paves the way for the elucidation of optimal design and operating parameters via modelling and optimisation [12,13].Dynamic modelling and optimisation of batch processes have been substantially implemented in the literature for a variety of bioprocesses, including fermentations [14,15], antibiotic synthesis [16,17] and many other applications, illustrating the utility and versatility of such methods in bioprocess design. Enzymatic synthesis, crystallisation and reactive crystallisation studies for β-lactam antibiotics have been implemented in the literature [16][17][18][19]. A demonstrated batch enzymatic synthesis of amoxicillin paves the way for theoretical studies [20]. Dynamic modelling and optimisation of the batch enzymatic synthesis of amoxicillin has yet to be implemented. Moreover, introducing temperature dependence into the model may allow for the optimisation of batch reactor temperature profiles to meet a specific production objective, which, to the best of our knowledge, has not been previously implemented.Processes 2019, 7, x FOR PEER REVIEW 2 of 17

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Waste Paper to Antibiotics: A Design and Feasibility Study of a Penicillin Production Facility in Trinidad and Tobago

Nunes

Maharaj

et al. 2019

Waste Biomass Valor

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Green Route for Amoxicillin Production Through the Integration With the Recycle of the by-Product (P-Hydroxyphenylglycine)

Cited by 3 publications

References 8 publications

Circular Economy Metrics for the Photo-High-p,T Continuous Multistep Synthesis of Vitamin D₃

Circular Economy Metrics for the Photo-High-p,T Continuous Multistep Synthesis of Vitamin D₃

Dynamic Modelling and Optimisation of the Batch Enzymatic Synthesis of Amoxicillin

Waste Paper to Antibiotics: A Design and Feasibility Study of a Penicillin Production Facility in Trinidad and Tobago

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Green Route for Amoxicillin Production Through the Integration With the Recycle of the by-Product (P-Hydroxyphenylglycine)

Cited by 3 publications

References 8 publications

Circular Economy Metrics for the Photo-High-p,T Continuous Multistep Synthesis of Vitamin D3

Circular Economy Metrics for the Photo-High-p,T Continuous Multistep Synthesis of Vitamin D3

Dynamic Modelling and Optimisation of the Batch Enzymatic Synthesis of Amoxicillin

Waste Paper to Antibiotics: A Design and Feasibility Study of a Penicillin Production Facility in Trinidad and Tobago

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Product

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Circular Economy Metrics for the Photo-High-p,T Continuous Multistep Synthesis of Vitamin D₃

Circular Economy Metrics for the Photo-High-p,T Continuous Multistep Synthesis of Vitamin D₃